Search

Background: It is well-established that spermatogenesis, semen quality, and reproductive hormones are interlinked. It is, however, less well-described how various specific testicular histopathologies are linked to reproductive hormones and semen quality., Objectives: To describe the detailed relationship between specific testicular histopathologies and the serum concentrations of reproductive hormones and semen quality., Materials and Methods: Descriptive histological patterns on testicular biopsies from 4245 patients referred for andrological workup in our clinic between 1990 and 2022 were grouped according to a published histological coding system: (1) complete spermatogenesis (completeSPG, n = 3171), (2) reduced spermatogenesis (reducedSPG, n = 657), (3) heterogeneous (hetArrest, n = 226), and (4) homogeneous (homArrest, n = 191) spermatogenic arrest at the spermatocyte or spermatid stage. As a proxy for the number of spermatogonia, spermatocytes, and spermatids, immunohistochemical staining for MAGE-A4, PIWIL1, and TNP1 were quantified on a representative set of biopsies (n = 100). Serum concentrations of FSH, LH, T, SHBG, and inhibin B (n = 1813) and semen parameters (n = 833) were available., Results: Compared with the completeSPG group, the number of spermatogonia was only reduced in the hetArrest group, while the number of spermatocytes and spermatids were lower in all groups. All groups had significantly higher FSH and LH and lower T, free T, and inhibin B concentrations when compared with the completeSPG group, except for the homArrest group, where inhibin B was unaffected. The hetArrest group had the lowest number of germ cells, the most pronounced change in reproductive hormones, and the lowest sperm counts. We found a strong correlation between the number of germ cells present and the corresponding serum concentrations of FSH, LH, T, and inhibin B., Discussion and Conclusions: A histopathological pattern of heterogeneous spermatogenic arrest is associated with a more severe phenotype than a pattern of homogeneous arrest, and the group with reduced spermatogenesis showed the mildest phenotype., (© 2024 The Author(s). Andrology published by John Wiley & Sons Ltd on behalf of American Society of Andrology and European Academy of Andrology.)

The pathological diagnosis and treatment of azoospermia depend on precise identification of spermatogenic cells. Traditional methods are time-consuming and highly subjective due to complexity of Johnsen score, posing challenges for accurately diagnosing azoospermia. Here, we introduce a novel SC-YOLO framework for automating the classification of spermatogenic cells that integrates S3Ghost module, CoordAtt module and DCNv2 module, effectively capturing texture and shape features of spermatogenic cells while reducing model parameters. Furthermore, we propose a simplified Johnsen score criteria to expedite the diagnostic process. Our SC-YOLO framework presents the higher efficiency and accuracy of deep learning technology in spermatogenic cell recognition. Future research endeavors will focus on optimizing the model's performance and exploring its potential for clinical applications.

Neurotensin (NTS), a tridecapeptide of the gastrointestinal tract, has been implicated in the facilitation of lipid absorption on ingestion of a high-fat diet (HFD) especially via NTS receptors, NTSR1, NTSR2, and NTSR3, to cause lipid metabolic dysregulation and imbalance of the oxidant-antioxidant system. Oxidative stress induced a negative impact on reproductive function, affecting the reproductive organ and related reproductive hormones. The present study elucidated the efficacy of NTSR1 antagonist SR48692 in the modulation of HFD-induced reproductive impairment in male mice. Swiss albino mice (male, 23 ± 2 g) were maintained (6/group) for eight weeks; Group-I chow diet (CD), Group-II HFD, Group-III (HFD+SR48692 L ), Group-IV (HFD+SR48692 H ), Group-V (CD+SR48692 L ) and Group-VI (CD+SR48692 H ). SR48692 low (100 µg/kg b.w./SR48692 L ) and high-dose (400 µg/kg b.w./SR48692 H ) were given intraperitoneally for the last four weeks. Treatment with low-dose (SR48692 L ) to HFD-fed mice showed some efficacy in mitigating lipid dysregulation, oxidative stress, and reproductive impairment as evidenced by decreased triglycerides, total cholesterol, low-density lipoprotein cholesterol, leptin, and increased high-density lipoprotein cholesterol, increased antioxidant defense enzymes, reduction of histopathological scores in testis and increase in plasma level of LH, FSH and testosterone compared to that of HFD, but not up to CD. With the high-dose of antagonist (SR48692 H ) showed more adverse effects even from that of HFD. Treatment of both doses of SR48692 to CD-fed mice these effects become more extended. Less effectiveness of NTSR1 antagonist with the doses tried (low and high) in normalizing the lipid dysregulation and reproductive impairments might be due to the persistence of NTSR2/NTSR3-mediated lipid absorption., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cadmium (Cd), a heavy metal element, cumulates in the testis and can cause male reproductive toxicity. Although vitamin E (VE) as one of potential antioxidants protects the testis against toxicity of Cd, the underlying mechanism remained uncompleted clear. The aim of this study was to investigate whether the Nrf-2 pathway is involved with the protective effect of VE on testicular damages caused by sub-chronic Cd exposure. Thirty-two SD rats were divided into four groups and orally administrated with VE and/or Cd for 28 consecutive days: control group, VE group (100 mg VE/kg), Cd group (5 mg CdCl 2 /kg), and VE + Cd group (100 mg VE/kg + 5 mg CdCl 2 /kg). The results showed that 28-day exposure of Cd caused accumulation of Cd, histopathological lesions, and alternations of sperm parameters (elevated rate of abnormal sperm, decreased count of sperm, declined motility, and viability of sperm). Moreover, the rats exposed to Cd showed significant oxidative stress (increased contents of MDA and decreased levels or activities of T-AOC, GSH, CAT, SOD and GSH-Px) and inhibition of Nrf-2 signaling pathway (downregulation of Nrf-2, HO-1, NQO-1, GCLC, GCLM and GST) of the testes. In contrast, VE treatment significantly reduced the Cd accumulation, alleviated histopathological lesions and dysfunctions, activated Nrf-2 pathway, and attenuated the oxidative stress caused by Cd in the testes of rats. In conclusion, VE, through upregulating Nrf-2 pathway, could protect testis against oxidative damages induced by sub-chronic Cd exposure., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Varicocele adversely affects semen parameters. However, the effect of varicocele repair on the sperm retrieval rate and testicular histopathological patterns in men with nonobstructive azoospermia has not been widely reported. We retrospectively assessed the sperm retrieval rates and testicular histopathological patterns in men with nonobstructive azoospermia who were referred to the Urology Clinic in Dr. Cipto Mangunkusumo Hospital (Jakarta, Indonesia) and Bunda General Hospital (Jakarta, Indonesia) between January 2009 and December 2019. We compared patients who had undergone a surgical sperm retrieval procedure for assisted reproductive technology no earlier than three months after varicocele repair and those who had not undergone varicocele repair. The study included 104 patients (age range: 26-54 years), 42 of whom had undergone varicocele repair before the sperm retrieval procedure and 62 who had not. Motile spermatozoa were found in 29 (69.1%) and 17 (27.4%) patients who had undergone varicocele repair before the sperm retrieval procedure and those who had not undergone the repair, respectively (relative risk: 2.51; 95% confidence interval: 1.60-3.96; P < 0.001). A predicted probabilities graph showed consistently higher sperm retrieval rates for patients with varicocele repair, regardless of their follicle-stimulating hormone levels. Patients who underwent varicocele repair showed higher testicular histopathological patterns (P = 0.001). In conclusion, men with nonobstructive azoospermia and clinical varicocele who underwent varicocele repair before the sperm retrieval procedure had higher sperm retrieval rates compared to those who did not undergo varicocele repair., Competing Interests: None

Objective: Chronic hyperglycemia and overproduction of reactive oxygen species (ROS) are strong predictors of the development of reproductive complications of diabetes. The present study was conducted to determine the effects of crocin on biochemical parameters, oxidative stress, and sperm characteristics as well as testes histopathology in diabetic rats., Materials and Methods: Twenty-four rats were divided into the four groups as follows: control, untreated diabetic and two crocin (40 and 60 mg/kg/day)-treated diabetic groups. Diabetes was induced by injection of a single dose of streptozotocin (STZ, 60 mg/kg). Administration of crocin (intraperitoneally) was started three days after STZ injection and was continued until the 28 th day. At the end of the experiment, rats were anesthetized after weighing. Blood samples and epididymal sperm were subsequently collected to measure biochemical parameters (glucose and lipid profile), total oxidant and antioxidant status (TOS and TAS, respectively), oxidative stress index (OSI), and sperm characteristics (count, motility, and viability); also, testes were dissected out for histopathology examination., Results: Our result indicated that blood glucose, cholesterol, triglyceride, LDL cholesterol levels, as well as TOS, and OSI decreased, but body weight, sperm counts, motility and viability, as well as TAS and HDL levels increased significantly in the crocin-treated diabetic rats (P˂0.05). In testis sections from diabetic rats treated with crocin (40 and 60 mg/kg), seminiferous tubules exhibited normal shape and restoration of testis architecture was observed., Conclusion: Administration of crocin in the present study, ameliorated blood glucose, lipid abnormalities, oxidative stress, sperm characteristics and testis damage in STZ-diabetic rats., Competing Interests: Seyed Mersad Sefidgar, Mahmood Ahmadi-hamedani, Ashkan Jebelli Javan, Reza Narenji Sani, and Abbas Javaheri Vayghan declare that they have no conflict of interest.

Objective: We investigate the protective and therapeutic effects of ozone therapy (OT) in radiotherapy (RT)-induced testicular damage., Methods: Thirty healthy adult male Wistar rats divided into five groups consisting of six animals each as follows: (1) Control (C), (2) RT, (3) OT, (4) OT + RT, and (5) RT + OT group. Histopathological findings, Johnsen scores, thiobarbituric acid-reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) levels were evaluated., Results: RT caused a significant decrease in testicular weight and Johnsen score compared to the control group. In addition, TBARS level was significantly higher, whereas GSH, SOD, catalase, and GPx levels were significantly lower in the RT group when compared to the control group. Pre and postRT OT significantly increased GSH, SOD, catalase, and GPx levels and decreased TBARS level. Furthermore, testicular weight and Johnsen score were increased with OT., Conclusions: The present study showed that OT is protective and therapeutic in radiation-induced testicular damage. OT may be beneficial to the patients who underwent RT., Competing Interests: None

The present work was conducted to evaluate the genotoxic effect of carbon tetrachloride (CCl 4 ) in mouse bone marrow and male germ cells. The safety and the modulating activity of sage (Salvia officinalis L.) essential oil (SEO) against the possible genotoxic effect of CCl 4 were also evaluated. A combination of in vivo mutagenic endpoints was included: micronucleus (MN), apoptosis using dual acridine orange/ethidium bromide (AO/EB) staining, comet assay, chromosomal aberrations (CAs), and sperm abnormalities. Histological examination of testis tissues was also studied. The extracted SEO was subjected to gas chromatography-mass spectrometry (GC-MS) for identifying its chemical constituents. Safety/genotoxicity of SEO was determined after two consecutive weeks (5 days/week) from oral treatment with different concentrations (0.1, 0.2, and 0.4 mL/kg). For assessing genotoxicity of CCl 4 , both acute (once) and subacute i.p. treatment for 2 weeks (3 days/week) with the concentrations 1.2 mL/kg (for acute) and 0.8 mL/kg (for subacute) were performed. For evaluating the protective role of SEO, simultaneous treatment with SEO plus CCl 4 was examined. In sperm abnormalities, mice were treated with the subject materials for five successive days and the samples were collected after 35 days from the beginning of treatment. Based on GC-MS findings, 22 components were identified in the chromatogram of SEO. The results demonstrated that the three concentrations of SEO were safe and non-genotoxic in all the tested endpoints. Negative results were also observed in bone marrow after acute and subacute treatment with CCl 4. In contrast, CCl 4 induced testicular DNA damage as evidenced by a significant increase of CAs in primary spermatocytes, sperm abnormalities, and histological distortion of testis. A remarkable reduction in these cells was observed in groups treated with SEO plus CCl 4 especially with the two higher concentrations of SEO. In conclusion, SEO is safe and non-genotoxic under the tested conditions and can modulate genetic damage and histological alteration induced by CCl 4 in the testes.

The ameliorative role of Eruca sativa on some hormonal profile and testicular histopathology in male albino rats exposed to a sublethal dose of 1 mg/kg body weight (b.wt). Abamectin (Crater 3.37% EC) was evaluated. Eighteen male albino rats were divided into three groups: control group, Abamectin-treated group, and Abamectin + E. sativa-treated group. Rats of the second group were orally administrated 1 mg/kg b.wt. of Abamectin, the third group received a mixture of sublethal oral dose of Abamectin (1 mg/kg b.wt.) and E. sativa suspension (5 g/kg b.wt.) every 48 h for 28 days. At the end of the study, blood samples were collected from all groups to measure some hormonal parameters; also, rats were dissected and tissue sections from the testes were prepared and stained with hematoxylin and eosin for examination under light microscope. The results of the present study revealed a disturbance in the hormonal parameters and some testicular histopathological changes. In addition, administration of E. sativa might have a promising effect against Abamectin toxicity-induced disorders of thyroid hormones and impaired testicular functions, which were correlated with histopathological changes in the testes of male rats.

Objective: To investigate whether testicular histology influences the clinical outcomes of intracytoplasmic sperm injection (ICSI) in men with non-obstructive azoospermia (NOA)., Methods: We retrospectively analyzed the clinical data about 73 cases of NOA undergoing ICSI, including 105 ICSI cycles and 79 embryo transfer cycles. The infertility of the patients was attributed to male factors only or both male and female tube factors and the females' age was ≤38 years. Based on testicular histology, we divided the ICSI cycles into three groups: hypospermatogenesis (HS, n = 72), maturation arrest (MA, n = 21) and Sertoli cells only (SCO, n = 12). We recorded and analyzed the age of both the males and females, infertility duration, base follicle-stimulating hormone (FSH) level, dose and days of gonadotropin (Gn) administration, estradiol (E2) and progesterone (P) levels on the day of human chorionic gonadotropin (hCG) administration, endometrial thickness, number of metaphase II (MII) oocytes, and rates of fertilization, transferrable embryos, high-quality embryos, clinical pregnancy, and abortion., Results: The rates of fertilization, failed fertilization, transferrable embryos, and high-quality embryos, and the average number of transferred embryos were 67.03% (553/825), 9.52% (10/105), 85.66% (472/551), 35.03% (193/551), and 2.10, respectively, resulting in 44 pregnancies (55.70%) and 42 live births (53.16%), with no birth defects. No statistically significant differences were observed among the HS, MA and SCO groups in the mean age of the men and women, infertility duration, base FSH level, Gn dose, Gn days, E2 and P levels on the hCG day, endometrial thickness, or number of MII oocytes, nor in the rates of fertilization (68.51% vs 64.39% vs 61.45%), transferrable embryos (85.05% vs 90.48% vs 83.05%), or high-quality embryos (33.09% vs 41.67% vs 38.98%). The rates of clinical pregnancy and embryo implantation were higher in the HS (60.00% and 37.61%) and SCO (62.50% and 50.00%) than in the MA group (37.50% and 21.21%), but with no statistically significant differences (P >0.05)., Conclusions: Once testicular sperm is retrieved, desirable clinical outcomes can be achieved in ICSI for NOA patients, which is not affected by testicular histopathology.

The purpose of this study was to observe the clinical utility and the possible determinants in predicting sperm retrieval of salvage microdissection testicular sperm extraction (mTESE) for nonobstructive azoospermia (NOA) patients with failed conventional TESE at their first attempts. A total of 52 NOA males underwent salvage mTESE were recruited in this study. Related data, including age, BMI, the presence of Klinefelter's syndrome and varicocele, cryptorchidism, mean testicular volume, hormonal profile (total testosterone (TT), follicle-stimulating hormone (FSH), luteinising hormone (LH), inhibin B (INHB)), testicular histology and surgical duration, were collected and analysed. A multivariate logistic regression with likelihood ratio test revealed the following predictors of sperm retrieval: TT and testicular histology (chi-square of likelihood ratio = 26.42, df = 4, p < .005). A formula was also established using multivariate regression analysis in predicting sperm retrieval probability. A predicted probability of more than 71% was determined of the formula as the cut-off value in predicting sperm retrieval using receiver operating characteristics (ROC) analysis with a sensitivity and specificity 78.0% and 72.4% respectively. In conclusion, salvage mTESE is of clinical value in NOA males with failed TESE attempts, whereas the established formula could be useful in determining the proper salvage mTESE candidates., (© 2016 Blackwell Verlag GmbH.)

Context: Hyperthermia causes detrimental effects on the testes leading to fertility problems. Mallotus roxbhurghianus Muell. Arg. (Euphorbiaceae) is used in traditional medicine and possesses antioxidant property. However, the mechanisms remain unknown in the context of alleviative action of M. roxburghianus against heat stress., Objective: The objective of this study was to demonstrate the alleviating activity of M. roxburghianus and its mechanism in scrotal hyperthermia., Materials and Methods: Scrotal hyperthermia experiments were performed in three groups (n = 7 per group) consisting of (i) the control group (C) maintained at 22 °C for 30 min, (ii) the heat stress-induced group (HS), and (iii) the heat stress-induced M. roxburghianus-treated group (HSM - 400 mg/kg each) in a thermostatically controlled water bath at 43 °C for 30 min. Subsequent to the heat treatment HS group, rats were treated with saline p.o and methanol extract of M. roxburghianus was administered to the rats of HSM group along with their standard food for 14 d. Scrotal hyperthermic effects were evaluated., Results: Scrotal hyperthermia significantly (p < 0.0001) elevated malondialdehyde levels while decreasing the body and testes weights, serum testosterone, and antioxidant enzyme levels due to oxidative stress. Disorganisation of seminiferous tubules and arrest of spermatogenesis were observed in the HS group. The administration of methanol extract of M. roxburghianus (400 mg/kg) for 14 d after heat treatment significantly suppressed the lipid peroxidation, restored the antioxidant enzyme and testosterone levels, revived the spermatogenesis, and increased the cell proliferation activity in the HSM group., Discussion and Conclusion: The methanol extract of M. roxburghianus accelerates testicular recovery from the damaging influence of hyperthermia.

Ethnopharmacological Relevance: Mallotus roxburghianus is used for its antihyperglycaemic properties in Southeast Asia especially in Northeast India (Mizoram) and is also recognized in traditional medicine. About 90% of diabetic patients have been associated with reproductive impairments. The primary aim of this investigation is to examine the effects of diabetes on oxidative stress, steroidogenesis, histopathology, proliferation of germ cells with proliferative cell nuclear antigen (PCNA) and antioxidant status, and alleviative effect of M. roxburghianus on the testis dysfunction., Materials and Methods: Methanolic leaf extract of M. roxburghianus was given to male albino Wistar rats by oral gavage to study the acute toxicity. Phyto-chemical composition of the methanol extract of M. roxburghianus was analyzed by GC-MS. Male Wistar rats were divided into six groups with seven animals in each group: untreated control; M. roxburghianus methanolic extract control (MRME, 400mg/kg); Alloxan diabetic control group (150 mg/kg); diabetic with 100mg/kg MRME treatment; diabetic with 400mg/kg MRME treatment; and diabetic with glibenclamide (0.1mg/kg) treatment. Diabetes was induced by a single intraperitoneal injection of 150 mg/kg alloxan and was confirmed by testing fasting plasma blood glucose levels 5 days after injection. MRME was administered orally for 28 days. Body and testis weights, serum testosterone, testis malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), glutathione S transferase (GST) and protein levels were measured, and testis tissue was examined histopathologically and immunohistochemically (PCNA)., Results: No sign of mortality and organ toxicity was observed up to 3000 mg/kg in acute toxicity assay of MRME and inferred to be non-toxic and safe. Bergenin and betulinic acid are the major components of MRME with many biological activities. MRME treatment rendered significant increases in body weight, testis weight, testes-body weight ratio, down regulated the MDA levels, reduced the degeneration and disruption of seminiferous tubule structure, restored the antioxidant enzymes and serum testosterone levels, increased the PCNA activities and attenuated the testes injury., Conclusion: MRME treatment to diabetic rats improves diabetes induced oxidative damage in testis as well as provides protection to testis. Phenols (Bergenin) and terpenes (Betulinic acid) were the main compounds of MRME that show antioxidant and antidiabetic activities and indeed validated its traditional use in the management of diabetes related testicular impairment., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)